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Rivaroxaban reduces acute limb ischemia, but increases major bleeds after revascularization for PAD (VOYAGER PAD)
Clinical Question
In patients who have undergone lower extremity revascularization because of peripheral arterial disease, does daily rivaroxaban provide a net benefit?
Bottom line
There is, at best, a small net benefit to adding rivaroxaban to aspirin with or without clopidogrel following lower extremity revascularization. However, for every 2 episodes of limb ischemia prevented, one major bleeding episode is caused. The cost is approximately $480 per month in the United States (www.goodrx.com on 5/30/20) and $85 per month in Ontario, Canada (www.formulary.health.gov.on.ca). Even at the lower Canadian price, it will cost CAD$109,480 ($85 × 28 [months] × 46 [the number needed to treat]) to prevent one episode of limb ischemia. 1b
Reference
Study design: Randomized controlled trial (single-blinded)
Funding: Industry
Setting: Outpatient (any)
Synopsis
These investigators identified 6564 patients with symptomatic peripheral arterial disease who had undergone revascularization. The patients were randomized to receive rivaroxaban 2.5 mg twice daily or matching placebo. All patients also received aspirin 100 mg and approximately half were taking clopidogrel; two-thirds had undergone an endovascular procedure and one-third had open surgery. The patients' median age was 67 years, 74% were men, and less than 3% were Black. Groups were balanced at baseline and analysis was by intention to treat. Patients were followed up for a median of 28 months. The primary outcome was a composite of 5 (five!) things: acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, and death from cardiovascular causes. The composite outcome was less likely in the rivaroxaban group (15.5% vs 17.8%; P = .009; number needed to treat [NNT] = 44). This was driven primarily by less acute limb ischemia (4.7% vs 6.9%; P < .05; NNT = 46). There was no clinically or statistically significant difference in the other 4 outcomes, and there were numerically more cardiovascular deaths in the rivaroxaban group (6.1% vs 5.3%; HR 1.14; 95% CI 0.93 - 1.40). There was significantly more bleeding in the rivaroxaban group. The bleeding was or wasn't statistically significant depending on how you define it – for example, there was more major bleeding in the rivaroxaban group using the International Society on Thrombosis and Haemostasis definition (4.3% vs 3.1%; P = .007; number needed to treat to harm = 83) -- but the bleeding was clinically signficant by every definition. Death from any cause was higher in the rivaroxaban group, but this difference was not statistically significant (9.8% vs 9.1%). Fortunately, there was no difference in the likelihood of fatal or intracranial bleeding (17 vs 19 events).
Reviewer
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA